Our previous observation that injection of monoclonal antibodies (mAbs) that block acetylcholine receptor (AcChR) function results in an extremely severe form of "hyperacute" experimental myasthenia, support the hypothesis that anti-AcChR antibodies of this type play a significant role in myasthenia gravis and experimental myasthenia. To further test this hypothesis we will assess the effect on neuromuscular transmission of members of our present library of anti-AcChR mAbs and of new anti-AcChR and anti-peptide mAbs to be developed in Project 5 and the Scientific Core. In addition we will attempt to develop a new form of treatment of experimental myasthenia consisting of injection of epitope-mimicking peptides as a form of "blocking antigen". The effect of these mAbs on neuromuscular transmission and neuromuscular junction histology and biochemistry will be assessed both in vitro and in vivo. The methods to be used in this collaborative Project include clinical assessment, clinical electromyography, light and electron microscopy, intracellular endplate recordings, determination of muscle AcChR content, and serological analysis of subtypes of AcChR antibodies.